tbuckley/cabot-search huggingface dataset:
Perioperative or adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer: Quality of life results of the randomized phase II AIO-NEONAX trial.
Authors: Sina Buchholz, Thomas Jens Ettrich, Waldemar Uhl, Marko Kornmann, Hana Algül, Helmut Friess, Alexander Koenig, Eike Gallmeier, Manfred P. Lutz, Kai Wille, Carl Christoph Schimanski, Volker Kunzmann, Michael Geissler, Dirk Waldschmidt, Severin Daum, Lukas Perkhofer, Anke C. Reinacher-Schick, Thomas Seufferlein
Journal: Journal of Clinical Oncology (2023)

694 Background: Perioperative chemotherapy (CTX) in resectable pancreatic adenocarcinoma (rPDAC) is still not considered SoC and data regarding efficacy but also quality of life (QoL) are limited. NEONAX is a prospective, randomized phase II trial in patients with rPDAC with two independent experimental arms examining perioperative (2 pre- and 4 postoperative cycles, arm A) or adjuvant (6 cycles, arm B) of Gem (1000mg/m 2 ) and nab-P (125mg/m 2 ) on days 1,8,15 of a 28-day cycle. The primary endpoint DFS at 18 mo. as well as DFS, OS and safety have already been reported. Here we present the QoL data of the NEONAX trial. Methods: QoL was evaluated by EORTC QLQ-C30, EORTC QLQ-PAN26 and HADS-D questionnaires at baseline, at the beginning of each CTX cycle (neoadj. and adj. in arm A, only adj. in arm B), after neoadj. treatment in arm A as well as prior and post resection and after 6 cycles of CTX. Results: Global health status score (GHS-score) (QLQ-C30) showed no difference between baseline (t1) and the timepoint after 6 cycles of CTX (t2) in the perioperative arm A (66.7/100 at both timepoints). Here patients experienced the lowest GHS-score pre- and postoperatively (50/100 in both cases). Adjuvant arm B showed a deterioration in the GHS-score of 12.5 points from timepoint 1 to 2 (62.5/100 to 50.0/100). Here the lowest GHS-score was observed within 4 weeks post-surgery (41.7/100). Physical function score (QLQ-C30) was decreased by 6.7 points (86.7/100 to 80/100) in perioperative arm A and by 26.7 points (86.7/100 to 60/100) in arm B between both timepoints. Role function (QLQ-C30) was reduced by 16.7 points (83.3/100 to 66.7/100) in arm A and by 33.3 points (83.3/100 to 50/100) in arm B between both timepoints. In the remaining subscales of the used questionnaires the two arms of the trial showed comparable median scores over the whole study period. The number of submitted questionnaires at each timepoint varied but was at large comparable in both arms. Conclusions: QoL was largely preserved in the perioperative as well as the adjuvant arm of the NEONAX trial. GHS-score was lower pre-and postoperatively in arm A. The lowest GHS-score was observed postoperatively in the adjuvant arm B. QoL was restored at the end of the treatment period in the perioperative arm A and remained slightly reduced in arm B suggesting that QoL is not substantially impaired by perioperative treatment in rPDAC. Clinical trial information: NCT02047513 . [Table: see text]
A novel immune monitoring platform for patients with gastrointestinal cancer.
Authors: Mojun Zhu, Wen Wee Ma, Harry H. Yoon, Joleen M. Hubbard, Robert R. McWilliams, Haidong Dong
Journal: Journal of Clinical Oncology (2023)

424 Background: Understanding the impact of anticancer therapies on immune system is critical to successful design and incorporation of immunotherapies. We developed a novel immune monitoring platform that measures the relative amount of circulating effector T cells and antitumor cytotoxicity of circulating immune cells. We previously showed that this assay can differentiate patients’ clinical response to anti-PD-1 therapy. Here, we applied this assay to patients with gastric or gastroesophageal junction adenocarcinoma (GGEA) who received chemoradiation or chemotherapy-based therapies. Methods: Patients underwent peripheral blood collection at baseline and during follow-up. Levels of circulating effector T cells (CX3CR1+NKG7+/CD3+CD8+) were quantified by flow cytometry using peripheral blood mononuclear cells (PBMCs). Antitumor cytotoxicity of circulating immune cells was evaluated by co-culturing CD3/CD28 activated PBMCs with calcein-AM labeled GGEA tumor cells (FLO-1). Antitumor cytotoxicity of individual patients’ PBMCs was calculated based on the amount of calcein released by dead tumor cells. Results: In a pilot study of 8 patients with mismatch repair-proficient (pMMR) GGEA, the changes in the frequency of effector T cells appeared to be associated with radiographic response to treatment based on RECIST (3 partial response [PR], 3 stable disease [SD], and 2 progressive disease [PD]). The median interval between sequential blood collections was 64 days and an increase in effector T cells was observed in patients with PD. Antitumor cytotoxicity was evaluated in 4 patients who did not receive targeted therapies or immune checkpoint inhibitors. Two of these patients (a, b) had blood collected at the time of diagnosis (treatment naïve) and after neoadjuvant therapy. One developed pulmonary metastases after chemoradiation while the other had significant tumor shrinkage after chemotherapy. The decrease in antitumor cytotoxicity of PBMCs was less in the patient with PD (-19.4%) than the one with PR (-48.5%). Two patients (c, d) had blood collected twice while receiving the same chemotherapy for metastatic disease (not treatment naïve). The decrease in antitumor cytotoxicity of PBMCs was less in the patient with SD (-0.3%) than the one with PR (-14.5%). Conclusions: We demonstrated the feasibility of using PBMCs to monitor immune response to anticancer therapies. Our data raise the possibility that the amount of circulating effector T cells and antitumor cytotoxicity of PBMCs may be associated with tumor burden in patients with pMMR solid tumors. [Table: see text]
Outcomes of endoscopic resection for early gastric cancer in very elderly patients: A nationwide population-based study.
Authors: Tae Jun Kim, Hyuk Lee, Jae J. Kim
Journal: Journal of Clinical Oncology (2023)

403 Background: Few studies have investigated the long-term outcomes of endoscopic resection for early gastric cancer (EGC) in very elderly patients. The aim of this study was to determine the appropriate treatment strategy and identify the risk factors for mortality in these patients. Methods: Patients with EGC who underwent endoscopic resection from 2006 to 2017 were identified using National Health Insurance Data and divided into three age groups: very elderly (≥85 years), elderly (65–84 years), and non-elderly (≤64 years). Their long- and short-term outcomes were compared in the three age groups, and the survival in the groups was compared with that in the control group, matched by age and gender. We also evaluated the risk factors for long- and short-term outcomes. Results: A total of 8,426 patients were included in our study: 118 very elderly, 4,583 elderly, and 3,725 non-elderly. The overall survival (OS) and cancer-specific survival (CSS) rates were significantly lower in the very elderly group than in the elderly and the non-elderly groups. Congestive heart failure was negatively associated with CSS. A significantly decreased risk for mortality was observed in all groups (P-value &lt; 0.001). The very elderly group had significantly higher readmission and mortality rates within 3 months of endoscopic resection than the non-elderly and elderly groups. Further, cerebrovascular disease was associated with mortality within 3 months after endoscopic resection. Conclusions: Endoscopic resection for EGC can be helpful for very elderly patients, and it may play a role in achieving OS comparable to that of the control group.[Table: see text]
Cost-effectiveness of gemcitabine plus cisplatin with and without durvalumab in patients with advanced cholangiocarcinoma.
Authors: J. Alberto Maldonado, Tim F. Greten, M. Cecilia Monge B.
Journal: Journal of Clinical Oncology (2023)

498 Background: Based on the results from the TOPAZ-1 study, current standard of care treatment for patients with advanced biliary tract cancer is gemcitabine and cisplatin (Gem/Cis) plus durvalumab (Durva). The addition of Durva improved progression-free survival (PFS) and overall survival (OS) compared to Gem/Cis alone. Considering that the epidemiology of cholangiocarcinoma may indicate some racial and ethnic groups may have a higher incidence and poorer prognosis; we present a cost analysis of this new treatment option. Methods: We calculated the unit prices of Durva and Gem/Cis with the information provided by the LexiComp (accessed September 2022). The drug cost per cycle was calculated for each drug; assuming an average patient surface area of 1.9m 2 for men and 1.6m 2 for women. In both cases, the chosen vial was the same and, thus, pricing was the same. Costs of administration, adverse effect and follow up were excluded. As per the TOPAZ-1 study design, the first 8 cycles included either Durva (day 1) + Gem/Cis (days 1 and 8) or placebo (day 1) + Gem/Cis (days 1 and 8) every 3 weeks, followed by Durva or placebo alone every 4 weeks until disease progression. The total treatment cost was composed of the sum of all treatment cycles received on study. Cost per life year gained was calculated using the total cost per year in each group and treatment duration as the denominator. Results: Cost per cycle for Durva, Gem, and Cis was $13,797, $282, and $87, respectively. The patients in the TOPAZ-1 trial who were randomized to the Durva arm had a median treatment duration of 7.3 months while patients in the Gem/Cis arm had a median treatment duration of 5.8 months. PFS was similar with a median time of 7.2 months and 5.7 months, respectively. This difference in both treatment duration and PFS (both 1.5 months) was associated with an increased cost of $124,170 over the course of treatment for Durva + Gem/ Cis compared to Gem/Cis alone ($127,119 vs $2,949). Durva + Gem/Cis has a medication only cost of $1,655,604 per life year gained as compared to Gem/Cis alone. Total yearly cost by treatment arm was higher for the Durva + Gem/Cis group ($209,899 vs $2,949). Conclusions: Durvalumab combined with gemcitabine and cisplatin is associated with an increase of 1.5 months in both treatment duration and PFS without additional toxicity observed when compared to Gem/Cis alone; however, Durva + Gem/Cis was associated with a drug cost over 40 times higher when compared Gem/ Cis alone for first-line treatment of advanced biliary tract cancer. Further research should focus on cost-effective solutions to treat advanced cholangiocarcinoma.
Ten years of experience in patients with resected pancreatic tumors: Real-world data in a public institution in Peru.
Authors: Jackeline Macetas, Heberth Daniel Vallejos, Eder Christian Veramendi Cabana, Mariana Serrano, Cristian Pacheco, Victor Castro Oliden, Raul Mantilla, Paola Catherine Montenegro
Journal: Journal of Clinical Oncology (2023)

686 Background: In Peru, the incidence of pancreatic tumors is 3.59 per 100,000 inhabitants, being the ninth cause of death. The standard of treatment in the world is surgery, achieved in 13% of patients, with overall survival (OS) and disease-free survival (PFS) at 5 years of 10% and 34%, respectively. In our study, the different subtypes of pancreatic tumors that were resected by surgery, their clinical/pathological characteristics, OS and PFS were evaluated. Methods: A retrospective review was carried out, in patients older than 18 years, diagnosed and treated with first intention surgery, during 2010 - 2019. 36.9% were adenocarcinoma (AD), 36.2% solid pseudopapillary neoplasm, 20.6% serous cystadenoma, 3.5% intraductal papillary mucinous neoplasm, 2.1% mucinous cystic neoplasm, and 0.7% acinar cell carcinoma. The Kaplan Meir method was used to estimate OS and PFS, and the log-rank test to differentiate between estimated curves. Results: 141 patients with resected pancreatic tumors; 73.8% without comorbidities and 2.1% with Diabetes Mellitus. Jaundice at debut was present in 22.7%, of whom 60% were AD; with OS at 5 years, 23.7% of patients with jaundice vs 69.9% without jaundice, 55.3% of tumors were located in the head of pancreas, 78.8% were AD; an OS at 5 years of 50.1% vs 67.3% of not located in the head of the pancreas. According to staging (S), 14.2% S I, 43.3% S IIA, 20.6% S IIB, and 22% S III; 100% were AD in S IIB-III vs 8.9% non-AD, with OS at 5 years S III of 16.2% and IIB of 39.3%. OS and PFS at 5 years, in pancreatic tumors were 57.7% and 73.5%, respectively. For patients with AD, the OS and PFS were 22.9% and 36.9%, respectively. Conclusions: The study suggests that jaundice at debut, located in head of the pancreas, S IIB-III, are worse prognostic factor in our patients with pancreatic tumors, especially in AD. And our patients with resected AD, presents greater survival compared to literature, although more evidence is still required due to the type of study.
A multi-institutional, single-arm, phase II trial of neoadjuvant modified-FOLFIRINOX for resectable pancreatic ductal adenocarcinoma.
Authors: Choong-kun Lee, Ho Kyoung Hwang, Hei-Cheul Jeung, Hongjae Chon, Hyung Soon Park, Min Hwan Kim, Sung Hyun Kim, Mi-Suk Park, Chang Moo Kang, Hye Jin Choi
Journal: Journal of Clinical Oncology (2023)

715 Background: Various peri-operative treatments have been tested to increase the survival of localized PDAC. Even with superior survival among various disease extent of PDAC, resectable PDAC still shows poor outcomes with surgery followed by adjuvant chemotherapy. We report the result of a multi-institutional phase II trial of modified-FOLFIRINOX as neoadjuvant treatment for resectable PDAC. Methods: Treatment naïve pts with histologically confirmed resectable PDAC were enrolled. Resectability was confirmed by both CT and MRI according to NCCN resectability criteria (no arterial tumor contact to celiac axis, SMA or CHA; no tumor contact with SMV or PV or ≤180° contact without vein contour irregularity) in multidisciplinary team meeting. Patients received oxaliplatin 85mg/m 2 D1 + leucovorin 400mg/m 2 D1 + irinotecan 150mg/m 2 D1 + 5-FU 2,000mg/m 2 46h continuous infusion, every other week for 6 cycles (12 weeks). Response assessments were performed every 6 weeks using the RECIST criteria version 1.1. Baseline MRI, PET-CT scan, and pre-surgery MRI after 6 cycles were mandatory. The primary endpoint was R0 resection rate. Secondary endpoints included survivals, ORR, safety, resection rate, and correlative biomarker exploration. (NCT05066802). Results: Total of 27 pts were enrolled between May 2020 and Feb 2022. Among total 27 pts, 24 pts underwent curative aim surgery after neoadjuvant treatment (resection rate 88.9%), and 23 pts showed R0 resection (23/27=85.2%), meeting the primary endpoint. Among 27 pts, 19 pts (70.4%) completed the neoadjuvant treatment per protocol. The reasons for neoadjuvant treatment discontinuation included progression of the disease (n=3, 11.1%) and pts withdrawal (n=5, 18.5%). Among 19 patients who underwent surgery per protocol, only one patient was R1 resected (R0 resection rate=94.7%). As of Sep 1, 2022 (median follow-up duration = 15.2 months) 6 pts recurred after surgery (6/19=31.6%). Median recur-free survival was 18.7 months (95%CI 13.6-NR) and median OS was not reached (95%CI 17.6-NR) for the per protocol treated pts. Treatment-related AE (≥G3) occurred in 10 pts (37.0%) including 7 (25.9%) with neutropenia G3-4. Conclusions: Three months of neoadjuvant mFOLFIRINOX was feasible and tolerable for resectable PDAC. Larger randomized trial is needed to validate the impact of neoadjuvant chemotherapy for resectable pancreatic cancer and to find subgroup of pts who would get benefit most from the neoadjuvant treatment. Post hoc genomic analyses with paired pre-neoadjuvant treatment and surgical tissues are ongoing. Clinical trial information: NCT05066802 .
MicroRNAs (miRs) as biomarkers of resistance to trastuzumab in HER2-positive oesophago-gastric cancer: Sub-study within the Planning Treatment for Oesophago-Gastric Cancer—A Randomised Maintenance Therapy Trial (PLATFORM).
Authors: Hazel Lote, Florentia Mousoullou, George Vlachogiannis, Caroline Fong, Laura Satchwell, Clare Peckitt, Ruwaida Begum, Shannon Kidd, Susan Cromarty, Anderley Gordon, Charlotte Victoria Fribbens, David J. Watkins, Sheela Rao, Ian Chau, Naureen Starling, David Cunningham, Nicola Valeri
Journal: Journal of Clinical Oncology (2023)

419 Background: A predictive biomarker for resistance to trastuzumab in HER2 positive oesophago-gastric cancer would refine patient selection. Our preclinical studies suggest that patients with HIGH baseline plasma miR-148a-3p levels will experience shorter Overall Survival (OS), Progression Free Survival (PFS), and worse Progression Free Rates (PFR) than those with LOW plasma miR-148a-3p levels. Methods: This sub-study is a prospective biomarker analysis of baseline plasma samples for HER2 positive advanced oesophago-gastric cancer patients registered within Arm B1 of the Phase 2 open label, multicentre, randomised PLATFORM trial (NCT02678182). All HER2 positive patients assessable for clinical response and miR signatures were included. Copies of miR-148a-3p and miR-16 per ml of plasma were quantified using Digital Droplet Polymerase Chain Reaction (ddPCR). OS as primary endpoint for miR-148a-3p LOW (≤median) versus HIGH (&gt;median) was analysed using Kaplan-Meier curves and Cox model regression. Secondary endpoints were PFS and PFR. OS and PFS are from start of 1 st line therapy; PFR are from start of maintenance trastuzumab. Sensitivity analysis normalised miR-148a-3p to miR-16. Results: Of 63 patients with analysable lab samples and available survival data, normalisation was possible for 41 patients. Median follow-up was 38 months. There was no statistically significant relationship between OS and miR-148-3p copies/μl of ddPCR reaction LOW versus HIGH (n= 62, Hazard Ratio (HR) 0.98, p=0.933), PFS (n=62, HR 1.08, p=0.759) or PFR (n=31, Odds Radio (OR) 0.67, p=0.577). Normalised miR-148a-3p (NmiR-148a-3p) LOW versus HIGH demonstrated a statistically significant difference in PFR at 3 months (n=23, OR=0.11, p=0.027) but no difference in OS or PFS. A model adjusting for primary tumour site, metastatic disease and number of sites demonstrated a statistically significant difference in PFR at 3 months (aOR=0.03, p=0.029). Conclusions: Patients with HIGH NmiR-148-3p have 0.03 times the odds of being progression-free at 3 months than patients with LOW NmiR-148a-3p in this population, when adjusted for key factors. Limitations include small sample size and normalisation. Clinical trial information: NCT02678182 . [Table: see text]
Effects of losartan and vitamin D on outcomes in metastatic pancreatic adenocarcinoma.
Authors: Adam Adika, Dina Ioffe, Meghan Connors, Emily C. Duboy, Kristen A. Sorice, Jill Hasler, Shannon M. Lynch, Edna Cukierman, Sanjay S. Reddy, Igor A. Astsaturov, Efrat Dotan
Journal: Journal of Clinical Oncology (2023)

723 Background: Active modification of surrounding stroma is a critical mechanism of tumor cell growth in pancreatic ductal adenocarcinoma (PDAC). There is some early translational evidence that losartan (L) and vitamin D (D) may affect the tumor microenvironment and supportive stroma in PDAC to help restore a physically and biologically tumor-suppressive stroma. These effects of potentially stroma-modifying drugs have not been established in the clinical management of metastatic PDAC (mPDAC), where there have been limited advances in treatment and prognosis remains poor. Methods: This is a single center, retrospective analysis of patients with mPDAC treated at Fox Chase Cancer Center from 2010 to 2019. All data including L and D use were extracted from the medical record. Patient characteristics were compared across subgroups using Chi-square tests, Fisher’s exact tests, and Wilcoxon rank sum tests. The primary outcome was overall survival (OS) from the time of metastatic diagnosis. Kaplan-Meier curves and log-rank tests were used to compare unadjusted OS across subgroups. Cox proportional hazards models were used to characterize OS adjusted for age at metastatic diagnosis, sex, initial stage at diagnosis, performance status, Charlson Comorbidity Index (CCI), hypertension, and renal disease. Results: 518 patients were included; a majority were male (54.1%), White (82.4%), and diagnosed with de novo mPDAC (54.6%). About half of patients had hypertension (53.5%) and few had renal dysfunction (5.6%). 153 (29.5%) patients were taking D and 41 (8%) patients were taking L. Women were more likely to take D than men (p &lt; 0.001) and White patients were more likely to take L than other races/ethnicities (p = 0.006). Median OS since metastatic diagnosis for patients taking L was 11.4 months compared to 9.6 months for patients not taking L (p = 0.07). Median OS for patients taking D was 11.3 months compared to 8.7 months for those not taking D (p = 0.10). A Cox proportional hazards model adjusting for confounders, however, showed that both L (HR 0.66, p = 0.02) and D (HR 0.81, p = 0.04) were significantly associated with improved OS from time of metastatic diagnosis. Conclusions: This large retrospective study demonstrates potential clinical and survival benefit of L and D in conjunction with mPDAC treatment. L and D are safe, well tolerated, and widely used in general medical practice. These results support further investigation of the stroma-modifying potential of L and D, as well as conducting prospective trials with these agents to further validate these findings.
AI-powered multi-omic signature to predict treatment response of patients with colorectal cancer liver metastasis.
Authors: Audrey Kapelanski-Lamoureux, Migmar Tsamchoe, Lucyna Krzywon, Jessica Bloom, Julie Cardin, Stephanie K Petrillo, Zu-hua Gao, Sarah Jenna, Anthoula Lazaris, Peter Metrakos
Journal: Journal of Clinical Oncology (2023)

252 Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in North America with over 50% of CRC patients developing liver metastases (LM) and 90% will die from metastatic disease. CRCLM are categorized into two main histological growth patterns (HGP) lesions: Desmoplastic (DHGP) and Replacement (RHGP). We have previously published that HGPs display distinct patterns of vascularization, local invasion, growth and response to treatment. Resected CRCLM patients with predominantly DHGP metastasis (~45%) receiving anti-VEGF therapy and chemotherapy have more than double the 5-year overall survival compared to patients with RHGP (~55%) who have received the same treatment. We are therefore treating patients that will not respond and should in fact be managed differently. Currently, there are no available biomarkers or stratification tools that predict colorectal cancer liver metastasis response to therapy. Methods: In collaboration with My Intelligent Machines (MIMs’), we used a proprietary GI2 (Genetic Interaction Graph Inference) algorithm inferring genetic interactions. We developed an AI based pipeline to develop a multi-modality signature, based on blood test analysis, to identify CRCLM patients who will 1) respond to Angiogenic Inhibitor-based therapies and 2) monitor the development of drug resistance (non-responders). Results: We obtained transcriptomic (tumor tissue) as well as proteomic data (liquid biopsy: Extracellular vesicle cargo), linked to clinical data from 40 chemonaïve patients, and fed the data into MIMs platform (BioMark). The software was able to identify differentially expressed genes common to the top differentially enriched proteins leading to a robust liquid biopsy biomarker signature distinguishing DHGP and RHGP. Furthermore, our data demonstrates a unique multi-modality signature providing biological insight for therapeutic failures and/or success. Conclusions: We will use these signatures to not only predict response to treatment but also decipher the molecular mechanisms driving these two phenotypes and identify unique targets. It is expected that this knowledge will lead to optimization of current treatment strategies, allowing for a precision therapy approach to the management of metastatic disease and cost saving for the health care system.